Indiana University-Purdue University Indianapolis (IUPUI) / CXXC finger protein 1 (CFP1) is an epigenetic regulator of H3K4 and cytosine
methylation. Due to its role in establishing and maintaining methylation patterns, CFP1
determines whether DNA is found in its euchromatin or heterochromatin state and as
such whether genes are transcriptionally active or inactive. In stem cells, deficiency of
CFP1 results in inability to differentiate and in murine embryos it results in periimplantation
death. Despite the demonstrated importance in developing tissue, the role of
CFP1 in mature tissues, such as the liver, has yet to be elucidated. This study examined
the role of CFP1 in maintaining liver homeostasis under conditions involving
hepatocellular stress by examining liver regeneration, pregnancy-induced hepatomegaly,
and non-alcoholic steatohepatitis (NASH) disease progression. The liver’s ability to
recover was analyzed through liver:body mass ratios, blood serum analysis, liver
histology, and qualitative observations. Deficiency of CFP1 in the livers of animals
subjected to partial hepatectomies (PH) resulted in decreased liver regeneration capacity
with liver mass restoration becoming significantly different starting at 48H post-PH and
remaining so until 10D post-PH. This decreased regeneration appeared to be the result of
reduced hepatocyte mitosis. Mouse dams lacking hepatic CFP1 mated with males
expressing CFP1 displayed a proclivity for dystocia. Mice subjected to a fast food diet
resulting in NASH while lacking hepatic CFP1 experienced decreased weight gain and
hepatic lipid accumulation compared to their CFP1 expressing counterparts. Through
these three studies, the critical role of CFP1 for the maintenance of liver homeostasis was
demonstrated.
| Identifer | oai:union.ndltd.org:IUPUI/oai:scholarworks.iupui.edu:1805/13634 |
| Date | 09 June 2017 |
| Creators | Chittajallu, Nandita |
| Contributors | Skalnik, David G. |
| Source Sets | Indiana University-Purdue University Indianapolis |
| Language | English |
| Detected Language | English |
| Type | Thesis |
| Rights | Attribution 3.0 United States, http://creativecommons.org/licenses/by/3.0/us/ |
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